3beta-dialkylaminoethoxy androstenes



United States Patent 3,151,133 3/3-DIALKYLAMINOETHOXY ANDROSTENES Edward W. Cantrall, Pearl River, Seymour Bernstein, New City, and Marvin J. Fahrenbach, Tornkins Cove, N.Y., assignors to American Cyanamid Company,

Stamford, Conn, a corporation of lllaine No Drawing. Filed Nov. 21, 1962, Ser. No. 239,347 8 Claims. (Ci. 260397.5)

This invention relates to new steroid compounds. More particularly, it relates to 3-substituted androstenes and androstadienes and methods of preparing the same.

The novel steroids of the present invention can be illustrated by the following formula:

wherein R and R are lower alkyl radicals,

C5-Ca is a C=CH or oH-0H2 wherein C C is as defined heretofore, with a compound of the formula:

(CH2) 1) Hal. RI!

wherein R, R" and n are as defined above and Hal. is halogen. The reaction is preferably carried out in a solvent inert to the reactants such as tetrahydrofuran in the presence of potassium t-butoxide. The reaction mixture is heated to a temperature within the range of from 50 C. to 110 C. for from minutes to 10 hours. Further treatment with a mineral acid produces the mineral acid salts.

Typical steroids prepared by the process of the present invention are: fi-dimethylaminoethoxy)-androst-5 ,16- diene; 3 B ('y-dimethylaminopropyloxy) -androst-5 l 6-diene; 3 B- (o-dimethylaminobutyloxy) -androst-5 l 6-diene; 3/5- ([3- diethylaminoethoxy)-androst-5,l6-diene; BB-(B-dipropyL aminoethoxy)-androst-5,16-diene; 3 p -diethylaminopropyloxy) -androst-16-ene; 3 [3- (fl-dimethylaminoethoxy) -androst-16-ene; 35- ('y-dipropylaminopropyloxy) -androst-16- ene; 3a-(fi-diethylaminoethoxy)-etiochol-16-ene; and the like. Methods of preparing these compounds are described hereinafter in the examples.

The steroid compounds of this invention have shown activity in lowering blood cholesterol. Compounds with this activity are useful in treating hypercholesteremia.

The following examples describe in detail the preparation of representative 3-substituted androstenes and androstadienes of the present invention.

EXAMPLE 1 Preparation of 3,8-(p-Dimethylaminoethoxy)-Alzdr0sta- 5,16-Diene To a solution containing 2.6 g. of androsta-5,l6-dien- 35-01 (J. Am. Chem. Soc., 77, p. 4145 (1955)). in 200 ml. of tetrahydrofuran is added 2.3 g. of potassium t-butoxide. The resulting mixture is heated to reflux with stirring under nitrogen for one hour. Dimethylaminoethyl chloride (6 ml.) is added dropwise over about one hour. The mixture is refluxed an additional three hours, cooled, filtered and evaporated to an oil (2.3 g.). The latter is dissolved in ether and treated with hydrogen chloride. The crude hydrochloride (0.98 g.) is partitioned between water and ether. The aqueous phase is basified and the product is collected by filtration to give 0.60 g., melting point 6467 C. A sample for analysis is recrystallized from acetone-water and has a melting point 65 -67 C.

EXAMPLE 2 Preparation of 3,8-(ti-dimethylaminoethoxy)-Andr0sta- 5,16-Diene Hydrochloride An ethereal solution of 3p-(B-dimethylarninoethoxy)- androsta-5,16,diene (Example 1) is treated with hydrogen chloride to give the product of the example.

EXAMPLE 3 Preparation of 3(3-("y-Diethylaminopropyloxy)- Andr0st-5 ,1 o-Diene Following the procedure of Example 1 and substituting 'y-diethylaminopropyl chloride for fi-dimethylaminoethyl chloride the product of the example is obtained.

EXAMPLE 4 Preparation of 3/3-(o-Diethylaminobutyloxy -Ana'r0st- 5,16-Diene Following the procedure of Example 1 and substituting E-diethylaminobutyl chloride for fi-dimethylaminoethyl chloride there is obtained the product of the example.

EXAMPLE 5 Preparation of 3,8-(B-Diethylaminoethoxy -A ndrosta- 5,1'6-Diene Following the procedure of Example 1 and substituting B-diethylaminoethyl chloride for fl-dimethylaminoethyl chloride the product of the example is obtained.

EXAMPLE 6 Preparation 0 f 3 3- (fl-Diethylaminoethoxy -A ndr0stl6-Ene Following the procedure of Example 1 and reacting fl-diethylaminoethyl chloride with 3fl-hydroxyandrost-l6- ene (Helv. 27, p. 66 (1944)) the product of the example is obtained.

EXAMPLE 7 Preparation of 3B-('y-Diethylaminopropyloxy)-Andr0st- J6-Ene Following the procedure of Example 1 and reacting 'y-diethylaminoethyl chloride with 3fi-hydroxyandrost-l6- ene give the product of the example.

'2 a We claim: 1. A compound selected from the group consisting of:

B Cu

in which R and R" are lower alkyl,

C5Cr1 is selected from the group consisting of .and n is an integer from 2 to 4, and its mineral acid salts.

2. The compound 3,8 (3 dimethy1aminoethoXy)-androsta-5,16diene.

3. The compound 3/3 ([3 diethylaminoethoxy) androsta-5,16-diene. 5 4. The compound 3,8-(B-diethylaminoethoxy)-androst- 16-ene.

5. The compound 3f3-('y-diethylaminopropyloxy)-androsta-5,l6-diene.

6. The compound 35 (6 diethylaminobutyloxy) an- 10 drosta-5,l6-diene.

7. The compound 3fi-( -diethylaminopropyloxy)-androst-lo-ene.

8. The compound 3,8 ([3 dimethylaminoethoxy)-an- 15 drosta-5,l6-diene hydrochloride.

No references cited. 

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF: 